Dicarbonyl-induced accelerated aging in vitro in human skin fibroblasts

Dicarbonyls glyoxal (GO) and methylglyoxal (MGO) produced during the autoxidation of reducing sugars are a source of macromolecular damage in cells. Since an accumulation of damaged macromolecules is a universal characteristic of aging, we have tested whether GO and MGO which cause oxidative damage to proteins and other macromolecules can bring about accelerated aging in normal human skin fibroblasts in vitro. A treatment of cells with 1.0 mM GO or 400 mu M MGO leads to the appearance of senescent phenotype within 3 days, as judged by the following criteria: morphological phenotype, irreversible growth arrest and G(2) arrest, increased senescence-associated beta-galactosidase (SABG) activity, increased H2O2 level, increased N-xi-(carboxymethyl)-lysine (CML) protein level, and altered activities of superoxide dismutase and catalase antioxidant enzymes. This experimental model of accelerated cellular aging in vitro can be useful for studies on testing the effects of various physical, chemical and biological conditions, including natural and synthetic molecules, for the modulation of aging.